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* School of Biochemistry and Immunology, Trinity College, Dublin, Ireland;
Northern Ireland Histocompatibility and Immunogenetics Laboratory, Belfast City Hospital, Belfast, Northern Ireland; and
Department of Structural Biology, Stanford University, Stanford, CA 94305
NK cells express both inhibitory and activatory receptors that allow them to recognize target cells through HLA class I Ag expression. KIR3DL1 is a receptor that recognizes the HLA-Bw4 public epitope of HLA-B alleles. We demonstrate that polymorphism within the KIR3DL1 receptor has functional consequences in terms of NK cell recognition of target. Inhibitory alleles of KIR3DL1 differ in their ability to recognize HLA-Bw4 ligand, and a consistent hierarchy of ligand reactivity can be defined. KIR3DS1, which segregates as an allele of KIR3DL1, has a short cytoplasmic tail characteristic of activatory receptors. Because it is very similar to KIR3DL1 in the extracellular domains, it has been assumed that KIR3DS1 will recognize a HLA-Bw4 ligand. In this study, we demonstrate that KIR3DS1 is expressed as a protein at the cell surface of NK cells, where it is recognized by the Z27 Ab. Using this Ab, we found that KIR3DS1 is expressed on a higher percentage of NK cells in KIR3DS1 homozygous compared with heterozygous donors. In contrast to the inhibitory KIR3DL1 allotypes, KIR3DS1 did not recognize HLA-Bw4 on EBV-transformed cell lines.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by an Irish Health Research Board Project grant.
2 Address correspondence and reprint requests to Dr. Clair Gardiner, School of Biochemistry and Immunology, Trinity College, Dublin 2, Ireland. E-mail address: clair.gardiner{at}tcd.ie
3 Abbreviations used in this paper: KIR, killer cell Ig-like receptor; ECD, extracellular domain; LILR, leukocyte Ig-like receptor; F, forward; R, reverse.
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